Myocardial infarction is the major cause of death in industrialized countries. Rupture of vulnerable atherosclerotic plaques is currently recognized as an important mechanism for acute myocardial infarction, which often results in sudden death. Recent advances in cardiovascular research have identified anatomic, biomechanical, and molecular features of atherosclerotic plaques that predispose them to rupture. In a majority of vulnerable plaques, these features include 1) the presence of activated macrophages at the shoulder or edge of the plaque, 2) a thin fibrous cap (<60 μm) and 3) a large lipid pool. The lipid pool is thought to apply force to the fibrous cap that causes it to become compromised. Once it is ruptured, the lipid enters the vessel lumen, causing thrombosis, arterial occlusion, myocardial ischemia, and infarction. In addition to lipid-rich plaques with a thin fibrous cap, other plaque types have been recently implicated as vulnerable plaques. These plaques contain a surface erosion where the intima has been denuded, leaving a rough surface at risk for causing platelet aggregation and acute thrombosis.
Coronary arteries that do not contain plaque have a layered structure consisting of an intima, media, and adventitia. A simple model of a lipid-rich plaque is a two layered structure consisting of a fibrous cap and an underlying lipid pool. Other atherosclerotic plaque types consist of one layer, either fibrous or calcified. Research indicates that the distinct layers present in atherosclerotic plaques have different scattering, absorption, and anisotropy coefficients. It is believed that the measurement of these parameters using light will enable characterization of plaque type in vivo and allow for the diagnosis of vulnerable plaques.
Cellularity of fibrous caps of atherosclerotic plaque, manifested by the infiltration of macrophages (average size 20-50 μm), is thought to weaken the structural integrity of the cap and predispose plaques to rupture. Macrophages, and other plaque related cells, produce proteolytic enzymes such as matrix metalloproteinases that digest extracellular matrix and compromise the integrity of the fibrous cap. Activated macrophages are strongly colocalized with local thrombi in patients who have died of acute myocardial infarction and are more frequently demonstrated in coronary artery specimens obtained from patients suffering from acute coronary syndromes compared with patients with stable angina. This evidence suggests that an imaging technology capable of identifying macrophages in patients would provide valuable information for assessing the likelihood of plaque rupture. Results from intracoronary OCT, recently performed in patients, have shown an improved capability for characterizing plaque microstructure compared with IVUS. To date, however, the use of OCT for characterizing the cellular constituents of fibrous caps has not been fully investigated.
It would be desirable to have a means for using remitted light to measure the optical properties of atherosclerotic plaques, determine plaque cap thickness or identify plaques with surface erosions and as a result assess coronary plaque vulnerability.
A method that detects plaques vulnerable to rupture could become a valuable tool for guiding management of patients at risk and may ultimately prevent acute events. Many different catheter-based methods are under investigation for the detection of vulnerable plaques. These methods include intravascular ultrasound (IVUS), optical coherence tomography (OCT), fluorescence spectroscopy, and infrared spectroscopy. While IVUS and OCT are used to obtain cross-sectional images of tissue, only OCT has been shown to have sufficient resolution to detect the presence of a thin fibrous cap. Fluorescence and infrared spectroscopy are methods that primarily detect the presence of lipids within the vessel wall. Of the four proposed techniques, only OCT has been shown to be capable of spatially resolving parameters directly responsible for plaque rupture.